Huber Heinrich J, Duessmann Heiko, Wenus Jakub, Kilbride Seán M, Prehn Jochen H M
Department of Physiology and Mental Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Biochim Biophys Acta. 2011 Apr;1813(4):608-15. doi: 10.1016/j.bbamcr.2010.10.004. Epub 2010 Oct 13.
Mitochondria are pivotal for cellular bioenergetics, but are also a core component of the cell death machinery. Hypothesis-driven research approaches have greatly advanced our understanding of the role of mitochondria in cell death and cell survival, but traditionally focus on a single gene or specific signalling pathway at a time. Predictions originating from these approaches become limited when signalling pathways show increased complexity and invariably include redundancies, feedback loops, anisotropies or compartmentalisation. By introducing methods from theoretical chemistry, control theory, and biophysics, computational models have provided new quantitative insights into cell decision processes and have led to an increased understanding of the key regulatory principles of apoptosis. In this review, we describe the currently applied modelling approaches, discuss the suitability of different modelling techniques, and evaluate their contribution to the understanding of the mitochondrial apoptosis pathway. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.
线粒体对细胞生物能量学至关重要，但也是细胞死亡机制的核心组成部分。基于假设的研究方法极大地推进了我们对线粒体在细胞死亡和细胞存活中作用的理解，但传统上一次只关注单个基因或特定信号通路。当信号通路显示出增加的复杂性且总是包括冗余、反馈回路、各向异性或区室化时，源自这些方法的预测就变得有限。通过引入理论化学、控制理论和生物物理学的方法，计算模型为细胞决策过程提供了新的定量见解，并增进了对细胞凋亡关键调控原则的理解。在这篇综述中，我们描述了当前应用的建模方法，讨论了不同建模技术的适用性，并评估了它们对理解线粒体凋亡途径的贡献。本文是名为“线粒体：致命细胞器”的特刊的一部分。
